A better understanding of genetic factors that influence the severity of cerebral palsy (CP) in children or their role in repair and recovery could lead to new, innovative treatments that mitigate disability and improve functional outcomes. Apolipoprotein E (APOE) is important in the brain for neuronal maintenance and repair after injury. APOE codes for three isoforms: epsilon 2, 3 and 4. The epsilon 4 allele has been associated with worse outcomes after brain injury in adults, but pilot work suggests that it may be protective in the developing brain. We will utilize the existing population-based Norwegian Cerebral Palsy Registry to examine the relationship between APOE genotype, specifically the epsilon 4 allele, and motor, cognitive, and communication function. In the most innovative aspect of this project, we will also explore the role of APOE regulatory genes, including TOMM40, in cerebral palsy severity. DNA will be extracted from banked dried blood specimens obtained through the Norwegian mandatory newborn metabolic screening program. Genotyping and data analysis will occur at the University of Virginia. Before a clinical trial of an APOE- or TOMM40-based therapeutic is undertaken, it is important to understand their role in recovery from brain injury. It may be opposite of that observed in adults. PUBLIC HEALTH RELEVANCE: This project combines expertise in childhood APOE research at the University of Virginia with an ongoing population-based cerebral palsy registry in Norway, an opportunity not available in the United States. It focuses on how polymorphisms of the Apolipoprotein E (APOE) and regulatory genes proximate to APOE, including the TOMM40 gene, may be involved in the pathogenesis of CP.